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31.
Mooney LA; Bell DA; Santella RM; Van Bennekum AM; Ottman R; Paik M; Blaner WS; Lucier GW; Covey L; Young TL; Cooper TB; Glassman AH; Perera FP 《Carcinogenesis》1997,18(3):503-509
Prior epidemiological evidence suggests that genes controlling the
metabolism of carcinogens and antioxidant/nutritional status are associated
with lung cancer risk, possibly through their ability to modulate DNA
damage by carcinogens. We performed a cross-sectional analysis of 159 heavy
smokers from a cohort of subjects enrolled in a smoking cessation program.
A total of 159 blood samples were analyzed to determine the relative
contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and
glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to
polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in
smokers was affected by genetic polymorphisms and nutritional status.
Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher
(2-fold, P < or = 0.03) levels of DNA damage than those without. In
parallel models, PAH-DNA adducts were inversely associated with plasma
levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P
= 0.09), and alpha- tocopherol (beta = -0.28, P = 0.21) in 159 subjects.
The association between smoking-adjusted plasma beta-carotene levels and
DNA damage was only significant in those subjects lacking the GSTM1
detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a
statistical interaction between beta-carotene and alpha-tocopherol; when
beta- carotene was low, alpha-tocopherol had a significant protective
effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was
high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly
correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with
retinol (r = 0.20, P = 0.0005). These results suggest that several
micronutrients may act in concert to protect against DNA damage and
highlight the importance of assessing overall antioxidant status. In
conclusion, a subset of smokers may be at increased risk of DNA damage and
possibly lung cancer due to the combined effect of low plasma
micronutrients and genetic susceptibility factors. The use of biological
markers to assess efficacy of interventions and to study mechanisms of
micronutrients is timely given the current debate regarding the use of
chemopreventive agents in high risk populations.
相似文献
32.
Cloning and characterization of DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1 总被引:3,自引:0,他引:3
van der Maarel SM; Scholten IH; Huber I; Philippe C; Suijkerbuijk RF; Gilgenkrantz S; Kere J; Cremers FP; Ropers HH 《Human molecular genetics》1996,5(7):887-897
In several families with non-specific X-linked mental retardation (XLMR)
linkage analyses have assigned the underlying gene defect to the
pericentromeric region of the X chromosome, but none of these genes have
been isolated so far. Here, we report on the cloning and characterization
of a novel gene, DXS6673E, that maps to Xq13.1, is subject to
X-inactivation and is disrupted in the 5' untranslated region by a balanced
X;13 translocation in a mentally retarded female. The DXS6673E gene is
highly conserved among vertebrates and its expression is most abundant in
brain. It encodes a hydrophilic protein of 1358 amino acids (aa) that does
not show sequence homology to other known proteins. A segment of this
protein consisting of neutral and hydrophobic aa with a proline residue in
every second position may represent a transmembrane domain. Almost complete
sequence identity was found between the 3' end of the DXS6673E gene and two
expressed sequence tags (ESTs) and between the 5' end of the DXS6673E gene
and a third EST. Moreover, weaker sequence similarity was observed between
coding regions and two other ESTs.
相似文献
33.
Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR 总被引:12,自引:2,他引:12
Cremers FP; van de Pol DJ; van Driel M; den Hollander AI; van Haren FJ; Knoers NV; Tijmes N; Bergen AA; Rohrschneider K; Blankenagel A; Pinckers AJ; Deutman AF; Hoyng CB 《Human molecular genetics》1998,7(3):355-362
Ophthalmological and molecular genetic studies were performed in a
consanguineous family with individuals showing either retinitis pigmentosa
(RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive)
inheritance of allelic defects, linkage analysis positioned the causal gene
at 1p21-p13 (lod score 4.22), a genomic segment known to harbor the ABCR
gene involved in Stargardt's disease (STGD) and age- related macular
degeneration (AMD). We completed the exon-intron structure of the ABCR gene
and detected a severe homozygous 5[prime] splice site mutation,
IVS30+1G->T, in the four RP patients. The five CRD patients in this
family are compound heterozygotes for the IVS30+1G- >T mutation and a
5[prime] splice site mutation in intron 40 (IVS40+5G- >A). Both splice
site mutations were found heterozygously in two unrelated STGD patients,
but not in 100 control individuals. In these patients the second mutation
was either a missense mutation or unknown. Since thus far no STGD patients
have been reported to carry two ABCR null alleles and taking into account
that the RP phenotype is more severe than the STGD phenotype, we
hypothesize that the intron 30 splice site mutation represents a true null
allele. Since the intron 30 mutation is found heterozygously in the CRD
patients, the IVS40+5G->A mutation probably renders the exon 40 5[prime]
splice site partially functional. These results show that mutations in the
ABCR gene not only result in STGD and AMD, but can also cause autosomal
recessive RP and CRD. Since the heterozygote frequency for ABCR mutations
is estimated at 0.02, mutations in ABCR might be an important cause of
autosomal recessive and sporadic forms of RP and CRD.
相似文献
34.
A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects 总被引:14,自引:0,他引:14
de Kok YJ; Bom SJ; Brunt TM; Kemperman MH; van Beusekom E; van der Velde- Visser SD; Robertson NG; Morton CC; Huygen PL; Verhagen WI; Brunner HG; Cremers CW; Cremers FP 《Human molecular genetics》1999,8(2):361-366
We analysed a Dutch family with autosomal dominant non-syndromic
progressive sensorineural hearing loss and mapped the underlying gene
defect by genetic linkage analysis to a 11.0 cM region overlapping the
DFNA9 interval on chromosome 14q12-q13. Clinically, the Dutch family
differs from the original DFNA9 family by a later age at onset and a more
clearly established vestibular impairment. A gene that is highly and
specifically expressed in the human fetal cochlea and vestibule, COCH
(previously described as Coch5B2 ), was mapped to the DFNA9 critical
region. Sequence analysis revealed a 208C-->T mutation in the COCH gene,
resulting in a Pro51Ser substitution in the predicted protein in all
affected individuals of the family but not in unaffected family members and
200 control individuals. The same mutation was also identified in three
apparently unrelated families with a similar phenotype, suggesting the
presence of a Dutch founder mutation. The function of COCH is unknown but
several characteristics of the protein point to a structural role in the
extracellular matrix. The mutant serine at position 51 is situated between
cysteines and possibly interferes with proper COCH protein folding or its
interaction with extracellular matrix proteins.
相似文献
35.
36.
黑翠碱甲和黑翠碱乙的化学结构 总被引:2,自引:0,他引:2
从黑水翠雀(Delphinium potaninii W.T.Wang)根中分得2个新的牛扁碱型C19-二萜生物碱(I和II),由光谱分析(1HNMR,13CNMR和MS)和化学方法,确定碱I为黑翠碱甲(potanidineA)、碱II为黑翠碱乙(potanidineB)。 相似文献
37.
Bernardes-Silva CF Damião AO Sipahi AM Laurindo FR Iriya K Lopasso FP Buchpiguel CA Lordello ML Agostinho CL Laudanna AA 《Digestive diseases and sciences》2004,49(10):1569-1574
The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) on intestinal permeability (IP) and reactive oxygen species (ROS) generation in indomethacin-induced enteropathy, a well-known experimental model of Crohn's disease. Seventy-eight male Wistar rats were randomly assigned to receive indomethacin, indomethacin + UDCA, or vehicles. Indomethacin induced a significant increase in the fraction of urinary excretion of 51Cr-EDTA following oral administration (7.9 +/- 1.3 vs 2.3 +/- 0.2%; P < 0.05) and lucigenin-amplified chemiluminescence in intestinal fragments ex vivo (10.1 +/- 1.9 vs 2.6 +/- 0.4 cpm x 10(3)/mg; P < 0.05) compared to controls. UDCA significantly reversed these effects (P < 0.05), without being incorporated in biliary bile acid composition (HPLC analysis). These findings support a local protective effect of UDCA in experimental ileitis by the modulation of intestinal barrier dysfunction and oxidative stress. In short, they provide insights into mechanisms of action of UDCA in intestinal inflammation and a new perspective on the treatment of Crohn's disease. 相似文献
38.
Lisa FP Ng Martin L Hibberd Eng-Eong Ooi Kin-Fai Tang Soek-Ying Neo Jenny Tan Karuturi R Krishna Murthy Vinsensius B Vega Jer-Ming Chia Edison T Liu Ee-Chee Ren 《BMC infectious diseases》2004,4(1):1-11
Background
Schistosoma mansoni and Plasmodium falciparum are common infections of school aged children in Kenya. They both cause enlargement of the spleen, but their relative contribution to the condition of splenomegaly remains unknown in areas where both infections are endemic. Here, we have investigated whether relatively high exposure to both infections has a clinically measurable effect on this condition.Methods
96 children aged 6–16 years living along a ten kilometre stretch and within 4 km south of a river that is a source of both S. mansoni and malaria infections were examined clinically for splenomegaly along the mid clavicular line (MCL) and mid axillary line (MAL). The survey was conducted outside the malaria transmission season. The consistency of the organ was recorded as soft, firm or hard. Mapping of the locations of houses and the course of the river was undertaken. Egg counts were mapped at the household level, as were IgG3 responses to Plasmodium falciparum schizont antigen (anti-Pfs IgG3), in order to identify areas with relatively high exposure to both infections, either infection or neither infection. ANOVA was used to test for differences in egg counts, IgG3 levels and the magnitude of spleen enlargement between these areas.Results
4 contiguous sectors were identified, one where anti-Pfs IgG3 responses and S. mansoni egg counts were both high, one where only anti-Pfs IgG3 responses were high, one where only egg counts were high, and one where both anti-Pfs IgG3 responses and egg counts were low. Spleen MAL and MCL values were significantly higher amongst children from the sector with highest IgG3 levels and highest egg counts but similar amongst children from elsewhere. Both egg counts and anti-Pfs IgG3 responses were significantly higher in children with MAL values >=4 cm. Hardening of spleens was associated with proximity of domicile to the river.Conclusions
Micro-geographical variation in exposure to S. mansoni and malaria infections can be exploited to investigate the chronic impact of these two infections. These results provide firm evidence that relatively high exposure to both infections exacerbates splenomegaly even outside the malaria transmission season. Major implications include assessing the burden of infection in school age-children. 相似文献39.
40.